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Reduced Imaging After Urinary Tract Infection: Are Benefits Accompanied by Adverse Risks?

Reduced Imaging After Urinary Tract Infection: Are Benefits Accompanied by Adverse Risks? Febrile urinary tract infections (UTIs) are among the most common serious bacterial illnesses in infants and young children. Urinary tract infection has a reported prevalence of 14% in febrile infants younger than 8 weeks1 and 5% in children with unexplained fever younger than 2 years.2 The introduction of antibiotics allowed treatment of these infections, and improved imaging modalities have resulted in detection and evaluation of a wide range of kidney and urinary tract disorders. What is less certain is the relationship between febrile UTIs and chronic kidney disease. Much of the renal damage previously thought to be the consequence of UTI has been shown by improved antenatal ultrasonography to be congenital renal hypodysplasia.3,4 The influence that various imaging techniques and treatment strategies have on long-term outcomes remains unclear, keeping in mind that vesicoureteral reflux (VUR) is a significant risk factor for scarring,5 the severity of scarring correlating with the severity of reflux.6 A strong association in infants and young children between febrile UTIs and urinary tract abnormalities resulted in the American Academy of Pediatrics publishing guidelines for investigation and management in 1999.7 They recommended that all infants and children up to 2 years of age undergo ultrasonography and voiding cystourethrogram (VCUG) following a first febrile UTI. Those with abnormal findings, VUR in particular, were recommended to commence antibiotic prophylaxis. The UK National Institute for Health and Clinical Excellence8 published guidelines in 2007 for the management of UTI in children that recommended a more selective approach to investigation, based on age and risk factors. In this issue of the Archives, Schroeder et al,9 having previously adhered to routine imaging according to the American Academy of Pediatrics guidelines,7 instituted a more selective approach adapted from the National Institute for Health and Clinical Excellence guidelines.8 They determined the impact of the change on imaging use, detection of VUR, antibiotic prophylaxis, and UTI recurrence. In addition, their article addressed the concern expressed by many regarding the extent to which the benefit of any diminution in follow-up and investigation of children following a first febrile UTI might result in adverse outcomes. In the past, studies concentrated on the prevalence of urologic abnormalities detected following investigation of febrile UTIs. Infants and young children were considered at risk, with VUR believed to predispose to subsequent infections, with ongoing damage resulting in hypertension and renal failure. Prophylactic antibiotics were considered likely to prevent progressive renal damage. As previously noted, congenital renal hypodysplasia is now recognized as more common than acquired pyelonephritic scarring as a cause of chronic kidney disease,4 with no reduction in end-stage chronic kidney disease rates, despite an intensive investigation and management approach.10 Furthermore, recent randomized controlled trials of antibiotic prophylaxis have demonstrated absent11-14 or marginal15 benefit for lesser grades of VUR, with 1 study demonstrating benefit in preventing recurrent UTI in girls with high-grade dilating VUR.16 Voiding cystourethography has been the single most contentious procedure in the evaluation of febrile UTIs. Those advocating the investigation cite a strong association between high-grade reflux and renal damage, arguing that an abandonment of routine VCUG risks missing children with severe reflux at risk of further damage. However, a systematic review and a meta-analysis demonstrated VUR to be a weak predictor of renal damage in children hospitalized with UTI.17 Those in support of a selective approach maintain that lower-grade reflux is not important, with high-grade dilating reflux likely to be detected when the febrile UTI is atypical in presentation or following abnormalities on ultrasonography. It is in these patients where intervention in the form of antibiotic prophylaxis may be of benefit.16 Schroeder et al9 noted a dramatic reduction in VCUGs following a febrile UTI under their selective algorithm from 99% down to 13% and a lesser but significant decrease in ultrasonography (99% down to 67%). At the same time, they demonstrated no significant difference in cases of high-grade (grades 4 and 5) VUR identified. A reduction in antibiotic prophylaxis from 27% to 3%, primarily due to lack of detection of lesser grades of VUR, was not associated with an increased incidence of recurrent UTI. The benefits of the selective approach as detailed by Schroeder et al included less trauma and reduced radiation dose associated with the VCUG, significant cost savings with reduced burden on the health system, less psychological stress, and reduction in the use of antibiotics with consequent bacterial resistance. The only apparent risk of this selective approach appears to be the possibility that, with increasing numbers, occasional cases of high-grade reflux that might benefit from intervention are missed until further infections have occurred. We agree with Schroeder et al that the benefits outweigh any risk. This article has some limitations; it was a retrospective study over 2 sequential periods with the focus on reflux rather than scarring. As a consequence, some data were lacking, and more importantly, while compliance with the established American Academy of Pediatrics protocol was almost 100%, that with the newer algorithm was reported as only fair. Of additional concern, polymicrobial urine cultures were generally treated and accepted as true UTIs while UTI recurrence within 6 months reflects only a short-term outcome. There remains a lack of consensus as to the optimal investigative approach and subsequent management of febrile UTI. Other alternatives have been suggested including the “top-down” approach,18 whereby VCUG is performed only when an acute technetium dimercaptosuccinic acid scan confirms acute pyelonephritis. A further alternative is to focus on those with scarring on a late technetium dimercaptosuccinic acid scan as at risk of long-term sequelae.19 As highlighted in a recent editorial in the Archives20: Advancement of the health of children and adolescents requires sophisticated, high-quality research in which RCTs [randomized controlled trials] are a keystone. Future prospective randomized controlled trials will hopefully lead to a further reduction in unnecessary imaging and improved outcomes. Back to top Article Information Correspondence: Dr Montini, Department of Pediatrics, Nephrology and Dialysis Unit, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi Bologna, Via Massarenti 11, Padiglione 13, 40138 Bologna, Italy (giovanni.montini@aosp.bo.it). Author Contributions:Study concept and design: Hewitt and Montini. Drafting of the manuscript: Hewitt and Montini. Critical revision of the manuscript for important intellectual content: Montini. Study supervision: Montini. Financial Disclosure: None reported. References 1. Lin DS, Huang SH, Lin CC, et al. Urinary tract infection in febrile infants younger than eight weeks of age. Pediatrics. 2000;105(2):E2010654980PubMedGoogle ScholarCrossref 2. Hoberman A, Chao HP, Keller DM, Hickey R, Davis HW, Ellis D. Prevalence of urinary tract infection in febrile infants. J Pediatr. 1993;123(1):17-238320616PubMedGoogle ScholarCrossref 3. Koyle MA, Elder JS, Skoog SJ, et al. Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation. Pediatr Surg Int. 2011;27(4):337-34621305381PubMedGoogle ScholarCrossref 4. Montini G, Tullus K, Hewitt IK. Febrile urinary tract infections in children. N Engl J Med. 2011;365(3):239-25021774712PubMedGoogle ScholarCrossref 5. Faust WC, Diaz M, Pohl HG. Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature. J Urol. 2009;181(1):290-29719013606PubMedGoogle ScholarCrossref 6. Clinical guidelines: vesicoureteral reflux. American Urological Association Web site. http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=vur2010. Accessed June 26, 2011 7. American Academy of Pediatrics Committee on Quality Improvement Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. 1999;103(4, pt 1):843-85210103321PubMedGoogle Scholar 8. National Collaborating Centre for Women's and Children's Health. Urinary tract infection in children: diagnosis, treatment and long-term management. http://www.nice.org.uk/nicemedia/pdf/CG54fullguideline.pdf. Published August 2007. Accessed May 12, 2011 9. Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med. 2011;165(11):1027-1032Google ScholarCrossref 10. Craig JC, Irwig LM, Knight JF, Roy LP. Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy? Pediatrics. 2000;105(6):1236-124110835063PubMedGoogle ScholarCrossref 11. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117(3):626-63216510640PubMedGoogle ScholarCrossref 12. Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol. 2008;179(2):674-67918082208PubMedGoogle ScholarCrossref 13. Pennesi M, Travan L, Peratoner L, et al; North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? a randomized, controlled trial. Pediatrics. 2008;121(6):e1489-e149418490378PubMedGoogle ScholarCrossref 14. Montini G, Rigon L, Zucchetta P, et al; IRIS Group. Prophylaxis after first febrile urinary tract infection in children? a multicenter, randomized, controlled, noninferiority trial. Pediatrics. 2008;122(5):1064-107118977988PubMedGoogle ScholarCrossref 15. Craig JC, Simpson JM, Williams GJ, et al; Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-175919864673PubMedGoogle ScholarCrossref 16. Brandström P, Esbjörner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial in children, III: urinary tract infection pattern. J Urol. 2010;184(1):286-29120488494PubMedGoogle ScholarCrossref 17. Gordon I, Barkovics M, Pindoria S, Cole TJ, Woolf AS. Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis. J Am Soc Nephrol. 2003;14(3):739-74412595511PubMedGoogle ScholarCrossref 18. Preda I, Jodal U, Sixt R, Stokland E, Hansson S. Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography unnecessary after urinary tract infection. J Pediatr. 2007;151(6):581-58418035134PubMedGoogle ScholarCrossref 19. Montini G, Zucchetta P, Tomasi L, et al. Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1. Pediatrics. 2009;123(2):e239-e24619139086PubMedGoogle ScholarCrossref 20. Rivara FP, Alexander D. Randomized controlled trials and pediatric research. Arch Pediatr Adolesc Med. 2010;164(3):296-29720194268PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Pediatrics & Adolescent Medicine American Medical Association

Reduced Imaging After Urinary Tract Infection: Are Benefits Accompanied by Adverse Risks?

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Publisher
American Medical Association
Copyright
Copyright © 2011 American Medical Association. All Rights Reserved.
ISSN
1072-4710
eISSN
1538-3628
DOI
10.1001/archpediatrics.2011.173
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Abstract

Febrile urinary tract infections (UTIs) are among the most common serious bacterial illnesses in infants and young children. Urinary tract infection has a reported prevalence of 14% in febrile infants younger than 8 weeks1 and 5% in children with unexplained fever younger than 2 years.2 The introduction of antibiotics allowed treatment of these infections, and improved imaging modalities have resulted in detection and evaluation of a wide range of kidney and urinary tract disorders. What is less certain is the relationship between febrile UTIs and chronic kidney disease. Much of the renal damage previously thought to be the consequence of UTI has been shown by improved antenatal ultrasonography to be congenital renal hypodysplasia.3,4 The influence that various imaging techniques and treatment strategies have on long-term outcomes remains unclear, keeping in mind that vesicoureteral reflux (VUR) is a significant risk factor for scarring,5 the severity of scarring correlating with the severity of reflux.6 A strong association in infants and young children between febrile UTIs and urinary tract abnormalities resulted in the American Academy of Pediatrics publishing guidelines for investigation and management in 1999.7 They recommended that all infants and children up to 2 years of age undergo ultrasonography and voiding cystourethrogram (VCUG) following a first febrile UTI. Those with abnormal findings, VUR in particular, were recommended to commence antibiotic prophylaxis. The UK National Institute for Health and Clinical Excellence8 published guidelines in 2007 for the management of UTI in children that recommended a more selective approach to investigation, based on age and risk factors. In this issue of the Archives, Schroeder et al,9 having previously adhered to routine imaging according to the American Academy of Pediatrics guidelines,7 instituted a more selective approach adapted from the National Institute for Health and Clinical Excellence guidelines.8 They determined the impact of the change on imaging use, detection of VUR, antibiotic prophylaxis, and UTI recurrence. In addition, their article addressed the concern expressed by many regarding the extent to which the benefit of any diminution in follow-up and investigation of children following a first febrile UTI might result in adverse outcomes. In the past, studies concentrated on the prevalence of urologic abnormalities detected following investigation of febrile UTIs. Infants and young children were considered at risk, with VUR believed to predispose to subsequent infections, with ongoing damage resulting in hypertension and renal failure. Prophylactic antibiotics were considered likely to prevent progressive renal damage. As previously noted, congenital renal hypodysplasia is now recognized as more common than acquired pyelonephritic scarring as a cause of chronic kidney disease,4 with no reduction in end-stage chronic kidney disease rates, despite an intensive investigation and management approach.10 Furthermore, recent randomized controlled trials of antibiotic prophylaxis have demonstrated absent11-14 or marginal15 benefit for lesser grades of VUR, with 1 study demonstrating benefit in preventing recurrent UTI in girls with high-grade dilating VUR.16 Voiding cystourethography has been the single most contentious procedure in the evaluation of febrile UTIs. Those advocating the investigation cite a strong association between high-grade reflux and renal damage, arguing that an abandonment of routine VCUG risks missing children with severe reflux at risk of further damage. However, a systematic review and a meta-analysis demonstrated VUR to be a weak predictor of renal damage in children hospitalized with UTI.17 Those in support of a selective approach maintain that lower-grade reflux is not important, with high-grade dilating reflux likely to be detected when the febrile UTI is atypical in presentation or following abnormalities on ultrasonography. It is in these patients where intervention in the form of antibiotic prophylaxis may be of benefit.16 Schroeder et al9 noted a dramatic reduction in VCUGs following a febrile UTI under their selective algorithm from 99% down to 13% and a lesser but significant decrease in ultrasonography (99% down to 67%). At the same time, they demonstrated no significant difference in cases of high-grade (grades 4 and 5) VUR identified. A reduction in antibiotic prophylaxis from 27% to 3%, primarily due to lack of detection of lesser grades of VUR, was not associated with an increased incidence of recurrent UTI. The benefits of the selective approach as detailed by Schroeder et al included less trauma and reduced radiation dose associated with the VCUG, significant cost savings with reduced burden on the health system, less psychological stress, and reduction in the use of antibiotics with consequent bacterial resistance. The only apparent risk of this selective approach appears to be the possibility that, with increasing numbers, occasional cases of high-grade reflux that might benefit from intervention are missed until further infections have occurred. We agree with Schroeder et al that the benefits outweigh any risk. This article has some limitations; it was a retrospective study over 2 sequential periods with the focus on reflux rather than scarring. As a consequence, some data were lacking, and more importantly, while compliance with the established American Academy of Pediatrics protocol was almost 100%, that with the newer algorithm was reported as only fair. Of additional concern, polymicrobial urine cultures were generally treated and accepted as true UTIs while UTI recurrence within 6 months reflects only a short-term outcome. There remains a lack of consensus as to the optimal investigative approach and subsequent management of febrile UTI. Other alternatives have been suggested including the “top-down” approach,18 whereby VCUG is performed only when an acute technetium dimercaptosuccinic acid scan confirms acute pyelonephritis. A further alternative is to focus on those with scarring on a late technetium dimercaptosuccinic acid scan as at risk of long-term sequelae.19 As highlighted in a recent editorial in the Archives20: Advancement of the health of children and adolescents requires sophisticated, high-quality research in which RCTs [randomized controlled trials] are a keystone. Future prospective randomized controlled trials will hopefully lead to a further reduction in unnecessary imaging and improved outcomes. Back to top Article Information Correspondence: Dr Montini, Department of Pediatrics, Nephrology and Dialysis Unit, Azienda Ospedaliero Universitaria Sant'Orsola-Malpighi Bologna, Via Massarenti 11, Padiglione 13, 40138 Bologna, Italy (giovanni.montini@aosp.bo.it). Author Contributions:Study concept and design: Hewitt and Montini. Drafting of the manuscript: Hewitt and Montini. Critical revision of the manuscript for important intellectual content: Montini. Study supervision: Montini. Financial Disclosure: None reported. References 1. Lin DS, Huang SH, Lin CC, et al. Urinary tract infection in febrile infants younger than eight weeks of age. Pediatrics. 2000;105(2):E2010654980PubMedGoogle ScholarCrossref 2. Hoberman A, Chao HP, Keller DM, Hickey R, Davis HW, Ellis D. Prevalence of urinary tract infection in febrile infants. J Pediatr. 1993;123(1):17-238320616PubMedGoogle ScholarCrossref 3. Koyle MA, Elder JS, Skoog SJ, et al. Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation. Pediatr Surg Int. 2011;27(4):337-34621305381PubMedGoogle ScholarCrossref 4. Montini G, Tullus K, Hewitt IK. Febrile urinary tract infections in children. N Engl J Med. 2011;365(3):239-25021774712PubMedGoogle ScholarCrossref 5. Faust WC, Diaz M, Pohl HG. Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature. J Urol. 2009;181(1):290-29719013606PubMedGoogle ScholarCrossref 6. Clinical guidelines: vesicoureteral reflux. American Urological Association Web site. http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=vur2010. Accessed June 26, 2011 7. American Academy of Pediatrics Committee on Quality Improvement Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. 1999;103(4, pt 1):843-85210103321PubMedGoogle Scholar 8. National Collaborating Centre for Women's and Children's Health. Urinary tract infection in children: diagnosis, treatment and long-term management. http://www.nice.org.uk/nicemedia/pdf/CG54fullguideline.pdf. Published August 2007. Accessed May 12, 2011 9. Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med. 2011;165(11):1027-1032Google ScholarCrossref 10. Craig JC, Irwig LM, Knight JF, Roy LP. Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy? Pediatrics. 2000;105(6):1236-124110835063PubMedGoogle ScholarCrossref 11. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117(3):626-63216510640PubMedGoogle ScholarCrossref 12. Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol. 2008;179(2):674-67918082208PubMedGoogle ScholarCrossref 13. Pennesi M, Travan L, Peratoner L, et al; North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? a randomized, controlled trial. Pediatrics. 2008;121(6):e1489-e149418490378PubMedGoogle ScholarCrossref 14. Montini G, Rigon L, Zucchetta P, et al; IRIS Group. Prophylaxis after first febrile urinary tract infection in children? a multicenter, randomized, controlled, noninferiority trial. Pediatrics. 2008;122(5):1064-107118977988PubMedGoogle ScholarCrossref 15. Craig JC, Simpson JM, Williams GJ, et al; Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-175919864673PubMedGoogle ScholarCrossref 16. Brandström P, Esbjörner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial in children, III: urinary tract infection pattern. J Urol. 2010;184(1):286-29120488494PubMedGoogle ScholarCrossref 17. Gordon I, Barkovics M, Pindoria S, Cole TJ, Woolf AS. Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis. J Am Soc Nephrol. 2003;14(3):739-74412595511PubMedGoogle ScholarCrossref 18. Preda I, Jodal U, Sixt R, Stokland E, Hansson S. Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography unnecessary after urinary tract infection. J Pediatr. 2007;151(6):581-58418035134PubMedGoogle ScholarCrossref 19. Montini G, Zucchetta P, Tomasi L, et al. Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1. Pediatrics. 2009;123(2):e239-e24619139086PubMedGoogle ScholarCrossref 20. Rivara FP, Alexander D. Randomized controlled trials and pediatric research. Arch Pediatr Adolesc Med. 2010;164(3):296-29720194268PubMedGoogle ScholarCrossref

Journal

Archives of Pediatrics & Adolescent MedicineAmerican Medical Association

Published: Nov 1, 2011

Keywords: urinary tract infections,diagnostic imaging

References

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